Advancing therapeutic targeting of the vulnerable plaque

Macrophages expressing high levels of CD11c and IRF5 are proinflammatory and associate with indices of plaque vulnerability. (A) Using a reverse translational approach, Edsfeldt et al. leveraged RNA-sequencing, CyTOF analyses, and plaque immunohistochemistry to identify macrophage-specific factors associated with plaque vulnerability in humans, supported by mechanistic studies in a murine model of inducible plaque rupture. (B) Symptomatic plaques (left side) displayed increased content of proinflammatory CD11c+ and IRF5-expressing macrophages, located around a larger necrotic core and in the rupture-prone shoulder region. These CD11chi showed increased expression of the proinflammatory chemokine genes CCL2, CCL3, and CCL4. In contrast, asymptomatic plaques show a smaller CD11c+ area, smaller necrotic cores, and increased expression of genes involved in clearance of apoptotic cells (MFGE8 and ITGB3). IHC, immunohistochemtristy; CYTOF, cytometry by time of flight; OLPS-DA, orthogonal least partial square discrimination analysis. Macrophages expressing high levels of CD11c and IRF5 are proinflammatory and associate with indices of plaque vulnerability. (A) Using a reverse translational approach, Edsfeldt et al. leveraged RNA-sequencing, CyTOF analyses, and plaque immunohistochemistry to identify macrophage-specific factors associated with plaque vulnerability in humans, supported by mechanistic studies in a murine model of inducible plaque rupture. (B) Symptomatic plaques (left side) displayed increased content of proinflammatory CD11c+ and IRF5-expressing macrophages, located around a larger necrotic core and in the rupture-prone shoulder region. These CD11chi showed increased expression of the proinflammatory chemokine genes CCL2, CCL3, and CCL4. In contrast, asymptomatic plaques show a smaller CD11c+ area, smaller necrotic cores, and increased expression of genes involved in clearance of apoptotic cells (MFGE8 and ITGB3). IHC, immunohistochemtristy; CYTOF, cytometry by time of flight; OLPS-DA, orthogonal least partial square discrimination analysis.